The long range goal of this project is to identify and analyze in sequential fashion, the principal and relivant tissue alterations which occur during the development of oral mucosal cancer induced by chemicals. Carcinogen-altered cells, chemically induced in hamster buccal pouch are being studied in whole-mounts of intact epithelium suitable for microscopic visualization of the entire basal layer. The whole mounts can be used for autoradiographic and histochemical study. Topical application of 7,12 dimethylbenzanthracene (DMBA) in mineral oil rapidly induce individual basal cells with histochemical activity for gamma-glutamyl transpeptidase (GGT). With continued DMBA application, the GGT stained cells rapidly proliferated into dicreet intraepithelial plaques of GGT activity, some of which persist for at least several months after carcinogen treatment is stopped. In an initial study approximately 35 percent of the epithelial neoplasms resulting from DMBA application have patchy GGT activity. The growth kinetics of the early GGT staining cells, their response to suspected promoting agents, and their possible relevance to the carcinogenic process are being investigated.